In general the goals are to understand at the metabolic and molecular level the pathogeneses of several specific inherited disorders of purine metabolism. Specifically we are interested in generating hypoxanthine guanine phosphorbosyl transferase deficient mice, understanding the molecular defect in a mutant purine nucleoside phosphorylase molecule, and increasing further the resolution of our understanding of the pathogenesis of the immunologic disorders associated with the inherited deficiency of purine nucleoside phosphorylase and adenosine deaminase in humans. The goals for the current year include expansion of our stock of HGPRTase determining the specific site in the mutant human purine nucleoside phosphorlyase molecule at which the insertion of an aberrant peptide occurs, and characterizing at the molecular level the regulation of mammalian ribonucleotide reductase by utilizing the numerous mutations in that enzyme which we have generated in clutured T-lymphoma cells.